The overall objectives of this research are to develop methods (1) for estimating vaccine and antiviral efficacy and effectiveness in the field and (2) for characterizing complex and long-term properties of vaccination in individuals and populations. The specific aims are: (1) To continue development of study designs and methods of analysis for using validation samples to correct for misclassified outcomes in vaccine studies. The goal is improved estimates of protective vaccine efficacy and of indirect, total, and overall effectiveness of vaccination strategies as well as designs for efficient, cost-effective studies. (2) To continue developing methods for joint estimation of protective effects, VES, and effects on infectiousness, VE|, of vaccination, and the analogous effects of antiviral agents on infection, AVES, disease, AVED, and infectiousness, AVE]. This includes further development of the augmented study design and the new mini-community design. (3) To develop methods to improve estimation of the protective effect of vaccination with the percontact vaccine efficacy for susceptibility, VESP. (4) To develop methods for causal inference for the effects of vaccination on post-infection endpoints such as severity of disease and ability to transmit to others. In addition, causal inference for vaccine effects when the assumption of noninterference between individuals is violated will be explored. (5) To explore interpretation of the protective effects of vaccination, VEs, when combining results across studies in different populations, taking into account different levels of baseline transmission and pre-existing immunity. Statistical approaches include likelihood inference, Bayesian methods, semiparametric methods, hierarchical models, and survival methods. The methods will be motivated by the design and analysis of studies of vaccines against influenza, pertussis, pneumococcus, HIV, meningitis, as well as other acute and childhood diseases and influenza antiviral prophylaxis.